IP Library Granted Patent US 8,569,325
Granted Patent B2
US 8,569,325 · App. 12/006,546 · Granted Oct 29, 2013

Method of treatment with coadministration of aspirin and prasugrel

Inventors: Fumitoshi Asai (Nishitokyo, JP); Atsuhiro Sugidachi (Kawasaki, JP); Taketoshi Ogawa (Tokyo, JP); Teruhiko Inoue (Ube, JP)
Assignees: Daiichi Sankyo Company, Limited; Ube Industries, Ltd.
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Quick Facts
Patent No.
US 8,569,325
App. No.
12/006,546
Granted
Oct 29, 2013
Kind
B2
Abstract

A method for the prevention of diseases caused by thrombus or embolus. The method is to separately administer 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine or a pharmaceutically acceptable salt thereof, and aspirin, in their pharmacologically effective amounts, to a warm-blooded animal.

Claims (44)

1. A method for preventing disease caused by thrombus or embolus, said method consisting of separately administering to a human in need of prevention of said disease:

(a) 2-acetoxy-5 -(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6 ,7-tetrahydrothieno[3,2-c]pyridine or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients, lubricants, binders, disintegrators, emulsifiers, stabilizers, corrigents and/or diluents, and

(b) aspirin, and one or more pharmaceutically acceptable excipients, lubricants, binders, disintegrators, emulsifiers, stabilizers, corrigents and/or diluents,

wherein said 2-acetoxy-5 -(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5 ,6,7-tetrahydrothieno[3,2-c]pyridine or the pharmaceutically acceptable salt thereof, and aspirin are administered in pharmacologically effective amounts to prevent said disease caused by thrombus or embolus by reducing thrombogenesis or by reducing platelet aggregation in said human, after both (a) and (b) have been administered.

2. The method according to claim 1 , wherein the pharmaceutically acceptable salt is 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride.

3. A method for treating a disease caused by thrombus or embolus, said method consisting of separately administering to a human in need of reduction of thrombogenesis or reduction of platelet aggregation:

(a) 2-acetoxy-5 -(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients, lubricants, binders, disintegrators, emulsifiers, stabilizers, corrigents and/or diluents, and

(b) aspirin, and one or more pharmaceutically acceptable excipients, lubricants, binders, disintegrators, emulsifiers, stabilizers, corrigents and/or diluents,

wherein said 2-acetoxy-5 -(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5 ,6,7-tetrahydrothieno[3,2-c]pyridine or the pharmaceutically acceptable salt thereof, and aspirin are administered in pharmacologically effective amounts to treat said disease caused by thrombus or embolus by reducing thrombogenesis or by reducing platelet aggregation in said human, after both (a) and (b) have been administered.

4. The method according to claim 1 , wherein said disease caused by thrombus or embolus is a cardiovascular or cerebrovascular disorder.

5. The method according to claim 1 , wherein said disease caused by thrombus or embolus is thromboembolism associated with atherosclerosis or diabetes mellitus.

6. The method according to claim 1 , wherein said disease caused by thrombus or embolus are unstable angina pectoris, cerebral ischemic insult or restenosis due to angioplasty, endarterectomy or stent therapy.

7. The method according to claim 3 , wherein the pharmaceutically acceptable salt is 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride.

8. A method for treating a patient undergoing stenting or angioplasty consisting of separately administering to said patient:

(a) 2-acetoxy-5 -(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3 ,2-c]pyridine or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients, lubricants, binders, disintegrators, emulsifiers, stabilizers, corrigents and/or diluents, and

(b) aspirin, and one or more pharmaceutically acceptable excipients, lubricants, binders, disintegrators, emulsifiers, stabilizers, corrigents and/or diluents,

wherein said 2-acetoxy-5 -(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5 ,6,7-tetrahydrothieno[3,2-c]pyridine or the pharmaceutically acceptable salt thereof, and aspirin are administered in pharmacologically effective amounts to reduce the incidence or severity of restenosis in said patient undergoing stenting or angioplasty, after both (a) and (b) have been administered.

9. The method according to claim 8 , wherein the pharmaceutically acceptable salt is 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3 ,2-c]pyridine hydrochloride.

10. The method according to claim 2 , wherein the 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3 ,2-c]pyridine hydrochloride, and aspirin are administered at separate times.

11. The method according to claim 1 , wherein the pharmacologically effective amounts are pharmacologically effective amounts for said 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3 ,2-c]pyridine hydrochloride and aspirin, individually.

12. The method according to claim 3 , wherein said disease caused by thrombus or embolus is a cardiovascular disorder.

13. The method according to claim 3 , wherein said disease caused by thrombus or embolus is thromboembolism associated with atherosclerosis or diabetes mellitus.

14. The method according to claim 3 , wherein said diseases caused by thrombus or embolus are unstable angina pectoris, or restenosis due to angioplasty, endarterectomy or stent therapy.

15. A method for reducing event rate of diseases caused by thrombus or embolus, said method consisting of separately administering to a human in need of reduction of said event rate of said diseases:

(a) 2-acetoxy-5 -(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3 ,2-c]pyridine or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients, lubricants, binders, disintegrators, emulsifiers, stabilizers, corrigents and/or diluents, and

(b) aspirin, and one or more pharmaceutically acceptable excipients, lubricants, binders, disintegrators, emulsifiers, stabilizers, corrigents and/or diluents,

wherein said 2-acetoxy-5 -(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5 ,6,7-tetrahydrothieno[3,2-c]pyridine or the pharmaceutically acceptable salt thereof, and aspirin are administered in pharmacologically effective amounts to said reduce event rate of said diseases caused by thrombus or embolus by reducing thrombogenesis or by reducing platelet aggregation in said human, after both (a) and (b) have been administered.

16. The method according to claim 15 , wherein the pharmaceutically acceptable salt is 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3 ,2-c]pyridine hydrochloride.

17. The method according to claim 15 , wherein said diseases caused by thrombus or embolus are selected from the group consisting of: diseases induced by platelet aggregation, cardiovascular disorders, cerebrovascular disorders, and thromboembolism caused by thromboembolization.

18. The method according to claim 15 , wherein said diseases caused by thrombus or embolus are selected from the group consisting of: stable or unstable angina pectoris, thromboembolism associated with atherosclerosis or diabetes mellitus, recurrent embolism after degradation of original thrombus, embolism, ischemia-induced dementia, peripheral arteriopathy, thromboembolization associated with hemodialysis or atrial fibrillation, and thromboembolization in vascular prosthesis or in bypass between the aorta and the coronary artery.

19. The method according to claim 15 , wherein said diseases caused by thrombus or embolus are diseases selected from the group consisting of stable or unstable angina pectoris, cerebral ischemic insult, and restenosis due to angioplasty, endarterectomy or stent therapy.

20. A method for reducing thrombotic cardiovascular or thrombotic cerebrovascular events in a human in need of reduction of said events, said method consisting of separately administering:

(a) 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients, lubricants, binders, disintegrators, emulsifiers, stabilizers, corrigents and/or diluents, and

(b) aspirin, one or more pharmaceutically acceptable excipients, lubricants, binders, disintegrators, emulsifiers, stabilizers, corrigents and/or diluents,

wherein said 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine or the pharmaceutically acceptable salt thereof, and aspirin are administered in pharmacologically effective amounts to reduce thrombotic cardiovascular or thrombotic cerebrovascular events by reducing thrombogenesis or by reducing platelet aggregation in said human, after both (a) and (b) have been administered.

21. The method according to claim 20 , wherein the pharmaceutically acceptable salt is 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3 ,2-c]pyridine hydrochloride.

22. The method according to claim 20 , wherein said method reduces thrombotic cardiovascular events in said human.

23. The method according to claim 20 , wherein said method reduces thrombotic cerebrovascular events in said human.

24. A method for reducing thrombogenesis or reducing platelet aggregation in a human, said method consisting of separately administering to said human:

(a) 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3 ,2-c]pyridine or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients, lubricants, binders, disintegrators, emulsifiers, stabilizers, corrigents and/or diluents, and

(b) aspirin, and one or more pharmaceutically acceptable excipients, lubricants, binders, disintegrators, emulsifiers, stabilizers, corrigents and/or diluents,

wherein said 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine or the pharmaceutically acceptable salt thereof, and aspirin are administered in pharmacologically effective amounts to reduce thrombogenesis or reduce platelet aggregation in said human, after both (a) and (b) have been administered.

25. The method according to claim 24 , wherein the pharmaceutically acceptable salt is 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3 ,2-c]pyridine hydrochloride.

26. The method according to claim 25 , wherein the 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3 ,2-c]pyridine hydrochloride, and aspirin are administered at separate times.

Assignments (3)
CORRECTIVE ASSIGNMENT TO CORRECT THE ADDRESS OF THE SECOND ASSIGNEE, UBE INDUSTRIES, LTD. PREVIOUSLY RECORDED ON REEL 020383 FRAME 0172. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Jan 26, 2009
From: ASAI, FUMITOSHI; SUGIDACHI, ATSUHIRO; OGAWA, TAKETOSHI; INOUE, TERUHIKO
To: SANKYO COMPANY, LIMITED; UBE INDUSTRIES, LTD.
Reel/Frame 022154/0239 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 7, 2008
From: SANKYO COMPANY, LIMITED
To: DAIICHI SANKYO COMPANY, LIMITED
Reel/Frame 021645/0572 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 3, 2008
From: ASAI, FUMITOSHI; SUGIDACHI, ATSUHIRO; OGAWA, TAKETOSHI; INOUE, TERUHIKO
To: SANKYO COMPANY, LIMITED; UBE INDUSTRIES, LTD.
Reel/Frame 020383/0172 →
Priority Claims (1)
JP 2000-392983 · Dec 25, 2000 · national
Continuity (3)
Division 10600266 · Jun 20, 2003
Continuation PCTJP0111201 · Dec 20, 2001
Related Publication 20080108589A1 · May 8, 2008